Critical Care Medicine
Relationship between failed mechanism of sevoflurane postconditioning-induced myocardial protection and dynamin-related protein 1 activity in diabetic rats
Fang Aili, Shi Gaoxiang, Han Chongfang, He Jiandong, Wang Xiang, Duan Yinglei
Published 2017-11-20
Cite as Chin J Anesthesiol, 2017,37(11): 1398-1401. DOI: 10.3760/cma.j.issn.0254-1416.2017.11.030
Abstract
ObjectiveTo evaluate the relationship between the failed mechanism of sevoflurane postconditioning-induced myocardial protection and the activity of dynamin-related protein 1(Drp1)in diabetic rats.
MethodsPathogen-free healthy adult male Sprague-Dawley rats, weighing 220-280 g, in which diabetes mellitus was induced by combination of high-fat and high-sucrose diet and intraperitoneal injection of streptozotoein 30 mg/kg, were studied.Sixty rats with diabetes mellitus were divided into 5 groups(n=12 each)using a random number table: sham operation group(group Sham), myocardial ischemia/reperfusion(I/R)group(group I/R), sevoflurane postconditioning group(group SP), Drp1 inhibitor mitochondrial division inhibitor-1(Mdivi-1)group(group M)and Mdivi-1 plus sevoflurane postconditioning group(group M-SP). Myocardial I/R was induced by occluding the left anterior descending branch of the coronary artery for 30 min followed by 120 min reperfusion except for group Sham.Mdivi-1 1.2 mg/kg was intraperitoneally injected at 15 min before ischemia in M and M-SP groups, and 2.5% sevoflurane was inhaled starting from 5 min of reperfusion in SP and M-SP groups.Blood samples were collected from the right internal jugular vein at 120 min of reperfusion for measurement of serum cardiac troponin I(cTnI)concentrations(by enzyme-linked immunosorbent assay). Rats were then sacrificed and myocardial specimens were obtained for determination of the myocardial infarct size(by TTC), cell apoptosis(by TUNEL), expression of Bax, Bcl-2 and activated caspase-3(by Western blot)and nicotinamide adenine dinucleotide(NAD+ )content(by spectrophotometry). Apoptosis index(AI)and Bax/Bcl-2 ratio were calculated.
ResultsCompared with group Sham, the percentage of myocardial infarct size, serum concentration of cTnI, AI and Bax/Bcl-2 ratio were significantly increased, the expression of activated caspase-3 was up-regulated, and the NAD+ content was decreased in the other four groups(P<0.05). Compared with group I/R, the percentage of myocardial infarct size, serum concentration of cTnI, AI and Bax/Bcl-2 ratio were significantly decreased, the expression of activated caspase-3 was down-regulated, and the NAD+ content was increased in group M-SP(P<0.05), and no significant change was found in the parameters mentioned above in SP and M groups(P>0.05). Compared with group SP, the percentage of myocardial infarct size, serum concentration of cTnI, AI and Bax/Bcl-2 ratio were significantly decreased, the expression of activated caspase-3 was down-regulated, and the NAD+ content was decreased in group M-SP(P<0.05), and no significant change was found in the parameters mentioned above in group M(P>0.05).
ConclusionThe failed mechanism of sevoflurane postconditioning-induced myocardial protection may be related to the activity of Drp1 in diabetic rats.
Key words:
Diabetes mellitus; Myocardial reperfusion injury; Anesthetics, inhalation; Apoptosis
Contributor Information
Fang Aili
Department of Anesthesiology, Shanxi Academy of Medical Sciences Shanxi Dayi Hospital, Taiyuan 030032, China
Shi Gaoxiang
Department of Anesthesiology, Shanxi Medical University, Taiyuan 030001, China
Han Chongfang
Department of Anesthesiology, Shanxi Academy of Medical Sciences Shanxi Dayi Hospital, Taiyuan 030032, China
He Jiandong
Department of Anesthesiology, Shanxi Academy of Medical Sciences Shanxi Dayi Hospital, Taiyuan 030032, China
Wang Xiang
Department of Anesthesiology, Shanxi Academy of Medical Sciences Shanxi Dayi Hospital, Taiyuan 030032, China
Duan Yinglei
Department of Anesthesiology, Shanxi Medical University, Taiyuan 030001, China